VITROCELL Application Note for Highly efficient and realistic application of aerosolized drugs to ­human cells of the respiratory tract under physiologic conditions

In inhalation therapy, drugs are deposited as aerosols on cells of the respiratory tract from the nasal or lung region. Physiologically realistic in vitro cell culture models of the pulmonary epithelium and the air-blood barrier as well as from the nasal region are commercially available. Recently, these models have been refined to mimic SARS-CoV-2 infections.

The surface dose and the spatial distribution on the membrane delivers important data for measuring dose-response relationships in toxicity studies. Image evaluation of transmission electron microscopy (TEM) samples is a highly sensitive method for determination of deposition. This paper reports the development and characterization of a novel holder for film coated TEM copper grids, which allows for sampling under identical geometric and ambient conditions as in a cell culture chamber.

This article provides a method for culturing and exposing the human bronchial epithelial cell line Calu-37 at the Air-liquid Interface that mimics realistic, repeated inhalation exposure conditions that can be used for toxicity testing. By applying a continuous airflow using the Automated Exposure System, the cell model can be exposed to a low concentration of particles over a longer time period, reflecting realistic exposure conditions. Characteristics of both the cell model and of the exposure system are essential for achieving a realistic inhalation exposure model that can be used for repeated exposures.

The model utilizes an air–liquid interface exposure device, VITROCELL Cloud, which PETA had awarded to the Heriot–Watt group in 2017 along with three other groups, in an attempt to support the development of non-animal toxicity testing methods.

The STL is working to develop an in vitro screening ALI model to assess the acute respiratory irritation potential for new chemicals. These experiments examined multiple aspects of the model, including different cell culture systems (A549 and EpiAirway), different exposure methods (dynamic vapor and liquid phase), and different post exposure periods, all using acrolein as a model respiratory irritant. The goal was to better understand the critical parameters of the cell systems and exposure methods to enable the development of a consistent screening model, while gaining clarity of the dosimetry.

This study characterizes a 3D in vitro alveolar tissue model comprised entirely of primary human cells to investigate its ability to predict pulmonary ﬁbrosis. The study demonstrated that the EpiAlveolar model recapitulates relevant lung phenotypes and functions and is stable at VITROCELL Cloud with repeated exposures over 3 weeks.